Joint MiRNA/mRNA Expression Profiling Reveals Changes Consistent with Development of Dysfunctional Corpus Luteum after Weight Gain

Bradford, Andrew P.; Jones, Kenneth L.; Kechris, Katerina; Chosich, Justin; Montague, Michæl J.; Warren, Wesley C.; May, Margaret C.; Al-Safi, Zain; Kuokkanen, Satu; Appt, Susan E.; Polotsky, Alex J.

doi:10.1371/journal.pone.0135163

Cited by 42 publications

(9 citation statements)

References 114 publications

(128 reference statements)

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“…RNA reads were mapped to the human genome sequence (hg38) using GSNAP. Transcript assembly and expression were calculated by Cufflinks, and analyzed for differential gene expression by ANOVA in R (Bradford, et al 2015; Trapnell, et al 2010). Whole exome sequencing reads were mapped to the reference human genome GRCh37 (hg19) using BWA (Li and Durbin 2010).…”

Section: Methodsmentioning

confidence: 99%

Development of new preclinical models to advance adrenocortical carcinoma research

Kiseljak-Vassiliades¹,

Zhang²,

Bagby³

et al. 2018

Endocrine-Related Cancer

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Adrenocortical cancer (ACC) is an orphan malignancy that results in heterogeneous clinical phenotypes and molecular genotypes. There are no curative treatments for this deadly cancer with 35% survival at five years. Our understanding of the underlying pathobiology and our ability to test novel therapeutic targets has been limited due to the lack of preclinical models. Here, we report the establishment of two new ACC cell lines and corresponding patient-derived xenograft (PDX) models. CU-ACC1 cell line and PDX were derived from a perinephric metastasis in a patient whose primary tumor secreted aldosterone. CU-ACC2 cell line and PDX were derived from a liver metastasis in a patient with Lynch syndrome. Short tandem repeat profiling confirmed consistent matches between human samples and models. Both exomic and RNA sequencing profiling were performed on the patient samples and the models, and hormonal secretion was evaluated in the new cell lines. RNA sequencing and immunohistochemistry confirmed the expression of adrenal cortex markers in the PDXs and human tumors. The new cell lines replicate two of the known genetic models of ACC. CU-ACC1 cells had a mutation in and secreted cortisol but not aldosterone. CU-ACC2 cells had a mutation and loss of consistent with the patient's known germline mutation causing Lynch syndrome. Both cell lines can be transfected and transduced with similar growth rates. These new preclinical models of ACC significantly advance the field by allowing investigation of underlying molecular mechanisms of ACC and the ability to test patient-specific therapeutic targets.

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Section: Methodsmentioning

confidence: 99%

Development of new preclinical models to advance adrenocortical carcinoma research

Kiseljak-Vassiliades¹,

Zhang²,

Bagby³

et al. 2018

Endocrine-Related Cancer

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show abstract

“…Samples were submitted to the University of Colorado Denver Genomic and Microarray Core and sequenced using the Illumina HiSeq4000 Platform and single-end reads (1×151). Reads generated were mapped to the mouse genome by gSNAP, expression derived by Cufflinks, and differential expression analyzed by ANOVA in R, as described previously ( Bradford et al, 2015 ). DAVID ( Huang et al, 2009a , b ), with default parameters, was used for functional annotation clustering of significantly upregulated and downregulated genes.…”

Section: Methodsmentioning

confidence: 99%

Increased FGF8 signaling promotes chondrogenic rather than osteogenic development in the embryonic skull

Schmidt

Taiyab

Melvin

et al. 2018

Disease Models &Amp; Mechanisms

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The bones of the cranial vault are formed directly from mesenchymal cells through intramembranous ossification rather than via a cartilage intermediate. Formation and growth of the skull bones involves the interaction of multiple cell-cell signaling pathways, with fibroblast growth factors (FGFs) and their receptors exerting a prominent influence. Mutations within the FGF signaling pathway are the most frequent cause of craniosynostosis, which is a common human craniofacial developmental abnormality characterized by the premature fusion of the cranial sutures. Here, we have developed new mouse models to investigate how different levels of increased FGF signaling can affect the formation of the calvarial bones and associated sutures. Whereas moderate Fgf8 overexpression resulted in delayed ossification followed by craniosynostosis of the coronal suture, higher Fgf8 levels promoted a loss of ossification and favored cartilage over bone formation across the skull. By contrast, endochondral bones were still able to form and ossify in the presence of increased levels of Fgf8, although the growth and mineralization of these bones were affected to varying extents. Expression analysis demonstrated that abnormal skull chondrogenesis was accompanied by changes in the genes required for Wnt signaling. Moreover, further analysis indicated that the pathology was associated with decreased Wnt signaling, as the reduction in ossification could be partially rescued by halving Axin2 gene dosage. Taken together, these findings indicate that mesenchymal cells of the skull are not fated to form bone, but can be forced into a chondrogenic fate through the manipulation of FGF8 signaling. These results have implications for evolution of the different methods of ossification as well as for therapeutic intervention in craniosynostosis.

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“…Derived sequences were analyzed by the Anschutz Genomics Core Facility by applying a custom computational pipeline consisting of the open‐source gSNAP, Cufflinks, and R for sequence alignment and ascertainment of differential gene expression. In short, reads generated were mapped to the Drosophila genome (Bdgp5) by gSNAP, counts (FPKM) were derived by Cufflinks, and differential expression analyzed with ANOVA in R (Baird et al, ; Bradford et al, ; Maycotte et al, ; Wu and Nacu, ; Trapnell et al, ). A Q value of 0.01 was used as the cutoff for differential expression.…”

Section: Methodsmentioning

confidence: 99%

The RNA‐binding protein caper is required for sensory neuron development in Drosophila melanogaster

Olesnicky

Bono

Bell

et al. 2017

Developmental Dynamics

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Background Alternative splicing mediated by RNA-binding proteins (RBPs) is emerging as a fundamental mechanism for the regulation of gene expression. Alternative splicing has been shown to be a widespread phenomenon that facilitates the diversification of gene products in a tissue specific manner. Although defects in alternative splicing are rooted in many neurological disorders, only a small fraction of splicing factors have been investigated in detail. Results We find that the splicing factor Caper is required for the development of multiple different mechanosensory neuron subtypes at multiple life stages in Drosophila melanogaster. Disruption of Caper function causes defects in dendrite morphogenesis of larval dendrite arborization neurons, neuronal positioning of embryonic proprioceptors, as well as the development and maintenance of adult mechanosensory bristles. Additionally, we find that Caper dysfunction results in aberrant locomotor behavior in adult flies. Transcriptome-wide analyses further support a role for Caper in alternative isoform regulation of genes that function in neurogenesis. Conclusions Our results provide the first evidence for a fundamental and broad requirement for the highly conserved splicing factor Caper in the development and maintenance of the nervous system and provide a framework for future studies on the detailed mechanism of Caper mediated RNA regulation.

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Joint MiRNA/mRNA Expression Profiling Reveals Changes Consistent with Development of Dysfunctional Corpus Luteum after Weight Gain

Cited by 42 publications

References 114 publications

Development of new preclinical models to advance adrenocortical carcinoma research

Development of new preclinical models to advance adrenocortical carcinoma research

Increased FGF8 signaling promotes chondrogenic rather than osteogenic development in the embryonic skull

The RNA‐binding protein caper is required for sensory neuron development in Drosophila melanogaster

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